Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (807 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An indan and piperidine derivative that acts as a selective and reversible inhibitor of acetylcholinesterase. Donepezil is highly selective for the central nervous system and is used in the management of mild to moderate dementia in alzheimer disease.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Donepezil Hydrochloride; 1-Benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine hydrochloride; Aricept; E 2020; E-2020; E2020; Eranz; Donepezilium Oxalate Trihydrate.
Where it fits in the MeSH classification
- Broader topics
- Indans; Piperidines
Related concepts
- Acetylcholinesterase
- Dementia
- Alzheimer Disease
Research landscape
PubMed indexes 3,237 records tagged with the MeSH heading “Donepezil” (counts retrieved 2026-10-31). 753 of them (23.3%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 1,215 records.
Reviews account for 458 records (14.1%) and meta-analyses for 77. Randomized controlled trials number 389 (12.0%) as a share of all records on the topic. Randomized trials make up a comparatively large share of this literature, which means many treatment questions have been tested directly.
Show the data
| Period | Records |
|---|---|
| through 1999 | 165 |
| 2000-2009 | 1,215 |
| 2010-2019 | 1,104 |
| 2020 onward | 753 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 458 | 14.1% |
| Meta-analyses | 77 | 2.4% |
| Randomized controlled trials | 389 | 12.0% |
Method: PubMed query "Donepezil"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Donepezil Regulates LPS and Aβ-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Aβ-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo.
- Closing excerpt
- Taken together, our findings indicate that donepezil significantly downregulates LPS- and Aβ-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (219 words)
The acetylcholinesterase inhibitors donepezil and rivastigmine have been used as therapeutic drugs for Alzheimer's disease (AD), but their effects on LPS- and Aβ-induced neuroinflammatory responses and the underlying molecular pathways have not been studied in detail in vitro and in vivo. In the present study, we found that 10 or 50 μM donepezil significantly decreased the LPS-induced increases in the mRNA levels of a number of proinflammatory cytokines in BV2 microglial cells, whereas 50 μM rivastigmine significantly diminished only LPS-stimulated IL-6 mRNA levels. In subsequent experiments in primary astrocytes, donepezil suppressed only LPS-stimulated iNOS mRNA levels. To identify the molecular mechanisms by which donepezil regulates LPS-induced neuroinflammation, we examined whether donepezil alters LPS-stimulated proinflammatory responses by modulating LPS-induced downstream signaling and the NLRP3 inflammasome. Importantly, we found that donepezil suppressed LPS-induced AKT/MAPK signaling, the NLRP3 inflammasome, and transcription factor NF-kB/STAT3 phosphorylation to reduce neuroinflammatory responses. In LPS-treated wild-type mice, a model of neuroinflammatory disease, donepezil significantly attenuated LPS-induced microglial activation, microglial density/morphology, and proinflammatory cytokine COX-2 and IL-6 levels. In a mouse model of AD (5xFAD mice), donepezil significantly reduced Aβ-induced microglial and astrocytic activation, density, and morphology. Taken together, our findings indicate that donepezil significantly downregulates LPS- and Aβ-evoked neuroinflammatory responses in vitro and in vivo and may be a therapeutic agent for neuroinflammation-associated diseases such as AD.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34638977 · DOI · PMC8508964
Reduced basal forebrain atrophy progression in a randomized Donepezil trial in prodromal Alzheimer's disease [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer's disease (AD) dementia.
- Closing excerpt
- Donepezil administered at a prodromal stage of AD seems to substantially reduce the rate of atrophy of the BFCS nuclei with highest concentration of cholinergic neurons projecting to the cortex (NbM), hippocampus and entorhinal cortex (Ch1/2).
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (153 words)
Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer's disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day). Reduced annual BFCS rates of atrophy were found in the Donepezil group compared to the Placebo treated arm. Secondary analyses on BFCS subregions demonstrated the largest treatment effects in the Nucleus Basalis of Meynert (NbM) and the medial septum/diagonal band (Ch1/2). Donepezil administered at a prodromal stage of AD seems to substantially reduce the rate of atrophy of the BFCS nuclei with highest concentration of cholinergic neurons projecting to the cortex (NbM), hippocampus and entorhinal cortex (Ch1/2).
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28916821 · DOI · PMC5601919
MARK4 Inhibited by AChE Inhibitors, Donepezil and Rivastigmine Tartrate: Insights into Alzheimer's Disease Therapy [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Microtubule affinity-regulating kinase (MARK4) plays a key role in Alzheimer's disease (AD) development as its overexpression is directly linked to increased tau phosphorylation.
- Closing excerpt
- This study signifies the implications of AChE inhibitors, RT, and DP in Alzheimer's therapy targeting MARK4.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (227 words)
Microtubule affinity-regulating kinase (MARK4) plays a key role in Alzheimer's disease (AD) development as its overexpression is directly linked to increased tau phosphorylation. MARK4 is a potential drug target of AD and is thus its structural features are employed in the development of new therapeutic molecules. Donepezil (DP) and rivastigmine tartrate (RT) are acetylcholinesterase (AChE) inhibitors and are used to treat symptomatic patients of mild to moderate AD. In keeping with the therapeutic implications of DP and RT in AD, we performed binding studies of these drugs with the MARK4. Both DP and RT bound to MARK4 with a binding constant (K) of 107 M-1. The temperature dependency of binding parameters revealed MARK-DP complex to be guided by static mode while MARK-RT complex to be guided by both static and dynamic quenching. Both drugs inhibited MARK4 with IC50 values of 5.3 μM (DP) and 6.74 μM (RT). The evaluation of associated enthalpy change (ΔH) and entropy change (ΔS) implied the complex formation to be driven by hydrogen bonding making it seemingly strong and specific. Isothermal titration calorimetry further advocated a spontaneous binding. In vitro observations were further complemented by the calculation of binding free energy by molecular docking and interactions with the functionally-important residues of the active site pocket of MARK4. This study signifies the implications of AChE inhibitors, RT, and DP in Alzheimer's therapy targeting MARK4.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32443670 · DOI · PMC7277793
Donepezil Research in Cognitive Impairment: A Bibliometric and Scientometric Analysis of Global Trends and Pharmacological Perspectives [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundCognitive impairment (CI) greatly affects global health and quality of life.
- Closing excerpt
- Future studies are expected to focus on individualized therapy, combination strategies, and underexplored CI subtypes, aiming to enhance the therapeutic potential and clinical value of donepezil.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (208 words)
BackgroundCognitive impairment (CI) greatly affects global health and quality of life. Donepezil, a widely used treatment for CI, particularly in Alzheimer's disease, has been extensively studied; however, a comprehensive bibliometric analysis summarizing global research trends remains limited.MethodsRelevant English-language articles and reviews published between 2000 and 2025 were retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer were employed to analyze publication trends, collaborative networks, journal distribution, co-citation patterns, and keyword co-occurrence.ResultsA total of 1907 publications were identified. The United States led in both output and citation impact, with the University of Toronto emerging as the most influential institution. The U.S. Department of Health and Human Services provided the greatest funding support. The Journal of Alzheimer's Disease was the primary publishing outlet, and Etsuro Mori was the most prolific and influential author. Keyword analysis revealed "Donepezil," "Alzheimer's disease," and "Mild cognitive impairment" as dominant terms. Recent hotspots-such as "acetylcholinesterase," "oxidative stress," "neuroinflammation," "tau protein," and "mechanism"-reflect a shift toward mechanistic and preclinical research.ConclusionResearch on donepezil for CI has shown consistent growth, evolving from clinical application toward mechanistic exploration and disease modification. Future studies are expected to focus on individualized therapy, combination strategies, and underexplored CI subtypes, aiming to enhance the therapeutic potential and clinical value of donepezil.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41668529 · DOI · PMC12891979
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis [5]
- Research article A review of clinical treatment considerations of donepezil in severe Alzheimer's disease [6]
- Research article Clinical efficacy and safety of donepezil in the treatment of Alzheimer's disease in Chinese patients [7]
- Research article Classics in Chemical Neuroscience: Donepezil [8]
- Research article An evaluation of memantine ER + donepezil for the treatment of Alzheimer's disease [9]
- Research article Butyrylcholinesterase Protein Ends in the Pathogenesis of Alzheimer's Disease-Could BCHE Genotyping Be Helpful in Alzheimer's Therapy? [10]
References
- Kim J, Lee HJ, Park SK, Park JH, Jeong HR, Lee S, et al.. Donepezil Regulates LPS and Aβ-Stimulated Neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 Signaling. . 2021. PMID 34638977 · DOI · PMC8508964
- Cavedo E, Grothe MJ, Colliot O, Lista S, Chupin M, Dormont D, et al.. Reduced basal forebrain atrophy progression in a randomized Donepezil trial in prodromal Alzheimer's disease. . 2017. PMID 28916821 · DOI · PMC5601919
- Shamsi A, Anwar S, Mohammad T, Alajmi MF, Hussain A, Rehman MT, et al.. MARK4 Inhibited by AChE Inhibitors, Donepezil and Rivastigmine Tartrate: Insights into Alzheimer's Disease Therapy. . 2020. PMID 32443670 · DOI · PMC7277793
- Wang W, Chen Y, Xiong Z, Wang Z, Ye W, Li X. Donepezil Research in Cognitive Impairment: A Bibliometric and Scientometric Analysis of Global Trends and Pharmacological Perspectives. . 2026. PMID 41668529 · DOI · PMC12891979
- Battle CE, Abdul-Rahim AH, Shenkin SD, Hewitt J, Quinn TJ. Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis. Cochrane Database Syst Rev. 2021. PMID 33704781 · DOI · PMC8407366
- Adlimoghaddam A, Neuendorff M, Roy B, Albensi BC. A review of clinical treatment considerations of donepezil in severe Alzheimer's disease. CNS Neurosci Ther. 2018. PMID 30058285 · DOI · PMC6489741
- Zhang N, Gordon ML. Clinical efficacy and safety of donepezil in the treatment of Alzheimer's disease in Chinese patients. Clin Interv Aging. 2018. PMID 30349215 · DOI · PMC6187917
- Brewster JT, Dell'Acqua S, Thach DQ, Sessler JL. Classics in Chemical Neuroscience: Donepezil. ACS Chem Neurosci. 2019. PMID 30372021 · DOI
- Calhoun A, King C, Khoury R, Grossberg GT. An evaluation of memantine ER + donepezil for the treatment of Alzheimer's disease. Expert Opin Pharmacother. 2018. PMID 30244611 · DOI
- Jasiecki J, Wasąg B. Butyrylcholinesterase Protein Ends in the Pathogenesis of Alzheimer's Disease-Could BCHE Genotyping Be Helpful in Alzheimer's Therapy?. Biomolecules. 2019. PMID 31601022 · DOI · PMC6843418
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.